Naturally occurring tumor cytotoxin (NTC) will be decomplexed from anti-idiotype and used in complement dependent cytotoxity tests. Serum from a panel of healthy donors with NTC activity and Cohn Fraction II (as a control) will be evaluated. These sera will be tested for cytotoxicity against cell lines from patients with melanoma, carcinoma of the colon or breast and sarcoma. The purpose is to determine the range of cytotoxicity against different tumors and variations in different NTC sources. Further studies will be done to characterize the antiglobulin in rheumatoid sera which promotes complexed NTC cytotoxicity (ACF). Since ACF positive sera also contains anti-idiotype antiglobulin against autologous NTC, it will first be necessary to separate autologous ACF and anti-idiotype. Chromatographic techniques will be employed using our knowledge that ACF displaces anti-idiotype from the NTC complex and that anti-idiotype binds preferentially to immobilized NTC. Studies using papain and pepein digestion will be done to see what part of the NTC and/or anti-idiotype (gG molecule(s) interacts with ACF. The significance of 7s NTC will be tested in vivo using human melanoma implants in athymic mice. Mice will be inoculated with melanoma cells preincubated with and without NTC. Mice will also receive melanoma cells and then weekly injections of NTC. Tumor growth and mouse survival will be evaluated.